Platelets play an important role in stopping hemorrhage caused by damage to blood vessel through coagulation to form thrombi. On the other hand, it has been known that, when vascular endothelium is injured or the blood vessel is narrowed as in the case of arteriosclerosis, platelets aggregate and trigger thrombus or embolus formation, causing ischemic diseases such as myocardial infarction, angina pectoris, ischemic cerebrovascular disorder, and peripheral vascular disease. Therefore, platelet aggregation inhibitors are administered for prevention and treatment of such ischemic diseases. Aspirin is one such platelet aggregation inhibitor that has been used for a long time, and the effects of aspirin have been demonstrated by APT (Antiplatelet Trialists' Collaboration) in which clinical test results obtained by administering aspirin to 100,000 patients had been subjected to metaanalysis (BMJ, vol. 308, pages 81-106, 1994). Aspirin, however, is known to cause side effects such as hemorrhage in gastrointestine or like organs, namely, the so-called “aspirin-induced ulcer”, and the side effect is not dose-dependent and occurs at a rate of about 1 per 100 patients (BMJ, vol. 321, pages 1183-1187, 2000).
The inhibitory effect of aspirin on platelet aggregation is known to be based on the activity to inhibit the action of cyclooxygenase. Cyclooxygenases include cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and aspirin specifically inhibits COX-1 at a low dose, resulting in inhibition of platelet aggregation. The inhibition of COX-1 also causes the aspirin-induced ulcer (Neurology, vol. 57, Suppl. 2, pages S5-S7, 2001 and Drugs Today, vol. 35, pages 251-265, 1999). In addition, nonsteroidal antiinflammatory drugs are known to exhibit antiinflammatory action by selectively inhibiting COX-2.
As described above, although aspirin is useful as a platelet aggregation inhibitor, it produces a side effect of gastrointestinal dysfunction attributable to the COX-1-inhibiting action, which is an action mechanism of platelet aggregation inhibition, and there is a strong demand for new platelet aggregation inhibitors exhibiting no COX-1-inhibiting activity.
In the meanwhile, as pyrazole derivatives having antithrombotic activity, there have been known compound (A) (Japanese Patent No. 2586713 and Chem. Pharm. Bull., vol. 45, pages 987-995, 1997) and compound (B) (BMJ, vol. 321, pages 1183-1187, 2000).
